Biologics Manufacturing from Gene to Product

With 35 years of experience in biomanufacturing, Richter-Helm BioLogics provides best-in-class solutions as a contract development and manufacturing organization (CDMO). We offer high-quality services from process and analytical method development to commercial manufacturing that is compliant with current good manufacturing practices (CGMPs). Such work requires expertise in process and analytical validation and process performance qualification (PPQ) to produce therapeutic proteins, peptides, antibody-like scaffolds, bacterial vaccines, and plasmid DNA (pDNA). Richter-Helm’s services are inspected routinely by regulatory authorities, such as the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA), to maintain high quality standards.

What sets us apart from other CDMOs is a strong customer focus. We think of our customers as partners, and we take their issues seriously. We give full attention to each product we manufacture to support our mission of providing high-level CDMO solutions to protect patient lives and improve public health.

Challenges and Possibilities

The biggest challenges in the biopharmaceutical CDMO business include tight timelines, unpredictable supply chains, constant development changes, and implementation of emerging tools such as artificial intelligence (AI). One of Richter-Helm’s great strengths is recognizing those trends and finding targeted, progressive solutions. Pharmaceutical companies are advancing several drug candidates in their pipelines to remain marketable. The goal is to limit risk associated with multiple technology transfers among several providers, which can lead to added time and costs. Therefore, outsourcing projects to a single CDMO partner is a growing trend. It offers promising opportunities for CDMO companies with respect to growth of business, implementation of new technological developments, digital transformation, establishment of expertise in certain areas, and building of strong and long-term partnerships.

The People Behind Your Product: Recruitment of qualified personnel and subject-matter experts for ongoing project success is another challenge for a CDMO. Qualified scientists, operators, laboratory staff, and project and business managers are in high demand. Our market reputation attracts talented staff who are eager to work in a growing, successful environment. All Richter-Helm teams are committed to addressing client needs. Our employees dedicate themselves to each individual project and promote a culture of open discussion and communication both within the company and with customers. Highly skilled and motivated people are the key to advancing projects successfully with flexibility and transparency.

Bringing Your Product to Success: Pharmaceutical companies increasingly use cutting-edge technologies to manufacture their products. Among these technologies are cell and gene therapy (CGT) approaches, for which the number of regulatory approvals continues to rise. Messenger RNA (mRNA) is another driver as a relatively new class of vaccines with promise for treating various diseases, including cancer. The plasmid DNA (pDNA) market also has experienced significant growth because of ongoing therapeutic developments. Plasmids are produced as critical raw materials and can serve as starting material for genetic applications — e.g., as DNA templates for CGTs. Plasmids are used also as active pharmaceutical ingredients (APIs) for vaccine applications. Richter-Helm offers an established, ready-to-use platform approach for manufacturing pDNA products at high yields (e.g., up to 2 g of plasmid/10 L of fermentation volume) and a maximum scale of 1,000 L (200 g of product). The high-performance proprietary RHB-pART process includes generic and validated quality testing with high purification success for plasmids in different matrices and at different sizes. For instance, supercoiled pDNA can be recovered at purities of ≥95%. The process is fully scalable between 10 L and 1,000 L of fermentation volume. Richter-Helm is the partner of choice for pDNA production and its supply in different grades, quantities, and applications.

Richter-Helm’s expanded manufacturing site in Bovenau, Germany.

Richter-Helm also has well-known experts in the microbial manufacture of protein-based APIs. Recombinant proteins in microbial and cell-free systems make up ~60% of our products. Recombinant protein manufacturing is one of the company’s core competencies, including the ability to make molecules such as nanobodies and fragment antigen-binding (Fab) regions. Strong advancements in drug-design tools have pushed the development of new therapeutic molecules into the protein-API market. The market will continue to develop and grow further as recombinant proteins are used in more treatments. Such drugs are manufactured predominantly in Escherichia coli and Pichia pastoris as microbial cell factories. Antibody-like scaffolds are gaining more attention because of their flexibility, small size, and potential application within the oncology field.

Evolving Market Demands and Expanding Capacities: Richter-Helm is reacting rapidly to emerging opportunities in the fast-moving pharmaceutical and bioprocessing sectors. By expanding its production capabilities as well as its development and analytical capacities, the company offers a reliable way to accelerate time to clinic and market, especially for large and commercial scales. The company’s new multipurpose facility is designed for maximum flexibility. It added a total area of ~10,000 m² and can accommodate projects of 300-L and 1,500-L fermentation volume, including mid- and downstream operations. The facility incorporates 100% oxygen aeration technology for high–cell-density fermentation in E. coli and yeast, which can provide higher product yields for proteins and pDNA. The new production lines use state-of-the-art equipment to produce multiple products simultaneously. The new site also includes additional space for large analytical laboratories, warehousing, technical areas for optimized personnel and material flow, and even room for further growth.

Richter-Helm has evolved from a small biotechnology company to an exceptionally trusted and valued partner for clients worldwide. New projects can start at Richter-Helm either from scratch with full development, as a transfer from an existing process for large-scale production or market supply, or for support with clinical studies. Richter-Helm continues to grow its capacities to offer reliable and highly specialized CDMO services for protein- and pDNA-based projects. That goal can be achieved through continuous improvement and innovation.

Thilo Kamphausen is director of business development ([email protected]), and Kai Pohlmeyer is managing director ([email protected]), both at Richter-Helm BioLogics GmbH & Co. KG, Suhrenkamp 59, 22335 Hamburg, Germany. For more information, visit https://www.richter-helm.eu.